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Completed

NCT Number: NCT01475669

Study of Fibrinogen Concentrate (Human) (FCH) to Control Bleeding During Complex Cardiovascular Surgery

The purpose of this study is to demonstrate that Fibrinogen Concentrate (Human)(FCH) can reduce the amount of donor blood products needed during complex cardiovascular surgery, and that it is safe and well tolerated. Subjects in this study will get either a FCH or placebo infusion during surgery. This will be in addition to the standard treatment, which is donor blood or blood products. Placebo does not contain any effective medicine.

The study is randomised. This means that the likelihood that subjects will get FCH or placebo is 50%. To make the comparison between FCH and placebo as fair as possible, the study is "double blind". This means that neither the subjects nor the study doctor will know if FCH or placebo is administered. If necessary, the study doctor can find out which treatment the subjects are receiving.

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Key information

Conditions

Surgical Blood Loss Blood Loss, Surgical Hemorrhage Intraoperative Complications Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Blood Loss Postoperative Complications Postoperative Hemorrhage

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Allgemeines Krankenhaus der Stadt Wien - Universitätskliniken, Vienna, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

At Screening:

  • Undergoing elective open surgical procedures on any part of the aorta requiring cardiopulmonary bypass (CPB), with or without other cardiac surgical procedures (e.g. valve replacement or repair, coronary artery bypass grafting, etc.).
  • 18 years of age or older.
  • Written informed consent for study participation obtained before undergoing any study specific procedures.

Intraoperative (at the 1st 5-minute bleeding mass):

  • A 5-minute bleeding mass of 60 to 250 g following discontinuation of CPB, administration of protamine, and establishment of surgical hemostasis.
  • Minimum core body temperature 35°C, measured according to local practice.
  • Activated clotting time ± 25% of baseline levels.
  • Blood pH > 7.3.

Exclusion criteria

At Screening and/or baseline:

  • Undergoing emergency aortic repair surgery.
  • Reoperative aortic surgery at the same anatomic site as the original procedure such as replacement of a previously placed aortic graft. Resternotomy and rethoracotomy are permitted.
  • Any operation for infection.
  • Proof or suspicion of a congenital or acquired coagulation disorder (e.g. Von Willebrand's disease, hemophilia or severe liver disease) or a prothrombotic disorder (e.g. protein C or S deficiency).
  • Myocardial infarction (MI), acute coronary syndrome or stroke in the 2 months preceding study surgery.
  • Low molecular weight or unfractionated heparin in the 24 hours preceding study surgery.
  • Clopidogrel administration within 5 days preceding study surgery or prasugrel administration within 7 days preceding study surgery or ticagrelor administration in the 48 hours preceding study surgery.
  • Factor Xa inhibitors within 2 days preceding study surgery.
  • IIb/IIIa antagonist administration in the 24 hours preceding study surgery.
  • Use of direct thrombin inhibitors: within 3 days preceding study surgery for dabigatran and within 24 hours preceding study surgery for all others.
  • An international normalized ratio > 1.3 immediately preceding the start of surgery.

Intraoperative (at the 1st 5-minute bleeding mass):

  • Use of any systemic hemostatic therapy (such as FFP, platelets, prothrombin complex concentrates) from the beginning of surgery until IMP administration.

Treatment and study plan

Fibrinogen Concentrate (Human) (FCH)

Biological

Single dose infused intravenously within 5 minutes of the completion of the measurement of the 5-minute bleeding mass; the dose is determined individually based on the measured maximum clot firmness (MCF) and subject body weight

Placebo

Biological

Single dose of sodium chloride solution infused intravenously within 5 minutes at a volume equivalent to that needed for FCH

Primary outcomes

  1. Total units of allogeneic blood products

    Time frame: Up to 24 hours after investigational medicinal product (IMP) administration

    Number of units administered of all allogeneic blood products combined (fresh frozen plasma, platelets, and red blood cells)

Secondary outcomes

  1. Total avoidance of allogeneic blood transfusions

    Time frame: 24 hours after IMP administration

    Number of subjects who are alive and do not have any administration of platelets, fresh frozen plasma (FFP), and red blood cells (RBCs) during the first 24 hours after administration of IMP

  2. Quantity of blood loss (6 hours)

    Time frame: 6 hours after skin closure

    Blood drainage volume from the chest

  3. Quantity of blood loss (12 hours)

    Time frame: 12 hours after skin closure

    Blood drainage volume from the chest

  4. Quantity of blood loss (24 hours)

    Time frame: 24 hours after skin closure

    Blood drainage volume from the chest

  5. Change in bleeding mass

    Time frame: Immediately before and 5 minutes after completion of IMP administration

    The 5-minute bleeding mass is measured as the difference in weight of surgical swabs after 5 minutes of surgical packing of the aortic surgical site.

  6. Mortality (Day 10)

    Time frame: Up to 10 days after surgery

    Mortality with adjudicated cause of death up to 10 days after surgery

  7. Mortality (Day 30)

    Time frame: Up to 30 days after surgery

    Mortality with adjudicated cause of death up to 30 days after surgery

  8. FFP consumption (24 hours)

    Time frame: 24 hours after IMP administration

  9. FFP consumption (10 days)

    Time frame: 10 days after IMP administration

  10. Platelet consumption (24 hours)

    Time frame: 24 hours after IMP administration

  11. Platelet consumption (10 days)

    Time frame: 10 days after IMP administration

  12. Red blood cells (RBC) consumption (24 hours)

    Time frame: 24 hours after IMP administration

  13. RBC consumption (10 days)

    Time frame: 10 days after IMP administration

  14. Total units of all allogeneic blood products (6 hours)

    Time frame: 6 hours after IMP administration

    Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP

  15. Total units of all allogeneic blood products (12 hours)

    Time frame: 12 hours after IMP administration

    Number of units of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP

  16. Volume of all allogeneic blood products (6 hours)

    Time frame: 6 hours after IMP administration

    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 6 hours after administration of IMP

  17. Volume of all allogeneic blood products (12 hours)

    Time frame: 12 hours after IMP administration

    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 12 hours after administration of IMP

  18. Volume of all allogeneic blood products (24 hours)

    Time frame: 24 hours after IMP administration

    Volume of all allogeneic blood products combined (FFP, platelets, and/or RBCs) administered during the first 24 hours after administration of IMP

  19. Time from administration of study drug to completion of skin closure

    Time frame: Average 2 hours

  20. Mortality (24 hours)

    Time frame: WIthin 24 hours after IMP administration

    Mortality with adjudicated cause of death during the first 24 hours after administration of IMP

  21. Peak plasma concentration of fibrinogen (Cmax)

    Time frame: At up to 10 time points from baseline and up to Day 11 after surgery.

  22. Maximum clot firmness

    Time frame: At baseline; on the day of surgery at: 30 min before CPB, the 1st 5 min bleeding mass, the end of IMP infusion, the 2nd 5-min bleeding mass, and closure; and on Day 2, 3, 4 and at the end of the study (discharge/Day 11 or at discontinuation if earlier).

Sponsors and collaborators

Lead sponsor

CSL Behring

Industry

Registry information

Official study title

REPLACE (Randomized Evaluation of Fibrinogen Versus Placebo in Complex Cardiovascular Surgery): a Prospective, Multinational, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study for the Use of Fibrinogen Concentrate (Human) (FCH) in Complex Cardiovascular Surgery

Acronym: REPLACE

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Nov 21, 2011
Registry last updated
Sep 18, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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